Novel non-invasive device for treatment of elevated intracranial pressures

描述（由申请人提供）： 据估计，美国每年有160万人头部受伤。创伤性脑损伤每年影响每1000个美国人中的3个，导致多达60，000人死亡，估计有70，000至90，000名患者患有永久性神经残疾。尽管在治疗头部损伤患者方面取得了进展，但创伤性脑损伤是儿童、成年人和军队士兵死亡和残疾的主要原因。这些伤害在生产力损失和医疗费用方面的经济后果是巨大的。虽然过去二十年的研究已经导致了对导致继发性神经元损伤的生理事件的更好理解，但在治疗颅内压升高和脑灌注减少的继发性脑损伤方面仍需要取得进展。申请人最近开发了一种新型装置，用于降低颅内压和增加脑灌注压。新的非侵入式设备插入患者和患者呼吸装置（例如机械呼吸机）之间的标准呼吸回路中。其通过在呼气阶段期间将胸内压降低至低于大气压水平和提供正压通气的手段之间循环来起作用。胸内压的降低（通常降低至-7至-9 mmHg）在胸腔内相对于身体的其余部分产生真空，从而a）增强血液返回心脏，并因此增加心输出量和血压，以及B）降低颅内压，从而增加脑灌注。使用胸内压力调节器（ITPR）旨在显著改善患者结局，其基于增加流向心脏和大脑的血流量的独特方式。1）通过证明在实质性和潜在致命性脑损伤后的第一个小时内使用ITPR有助于比单独使用标准复苏液更好地维持脑的代谢稳定性，在动物中确立了ITPR装置的安全性和概念证明;（二）将胸内压力真空计整合到ITPR系统中，并开始通过原型定制数字显示界面来开发闭环系统，该界面可跟踪重要的生理变量，颅内压和胸内压; 3）器械获得510 k许可。本II期研究申请旨在：1）证明临床概念的证据，即ITPR的应用将导致神经重症监护病房中头部损伤患者的颅内压降低和脑灌注压升高; 2）设计并制作ITPR的增强型可变真空版本原型，配备独立真空源和电源，用于OR和ICU。如果在这些II期研究中证明了显著的临床获益，ITPR有望提供一种全新的工具来增加脑灌注，从而降低颅内压升高患者（包括创伤性脑损伤和卒中患者）的发病率和死亡率。 公共卫生相关性： 尽管在头部损伤患者的治疗方面取得了进展，但创伤性脑损伤（TBI）是儿童和成人在其最具生产力的年龄段死亡和残疾的主要原因。它也是军队中发病率和死亡率的主要原因。据估计，美国每年有160万人头部受伤。创伤性脑损伤每年影响每1000个美国人中的3个，导致多达60，000人死亡，估计有70，000至90，000名患者患有永久性神经残疾。尽管在治疗头部损伤患者方面取得了进展，但创伤性脑损伤是儿童、成年人和军队士兵死亡和残疾的主要原因。这些伤害在生产力损失和医疗费用方面的经济后果是巨大的。虽然过去二十年的研究已经导致了对导致继发性神经元损伤的生理事件的更好理解，但在治疗颅内压升高和脑灌注减少的继发性脑损伤方面仍需要取得进展。申请人最近开发了一种新型装置，用于降低颅内压和增加脑灌注压。新的非侵入式设备插入患者和患者呼吸装置（例如机械呼吸机）之间的标准呼吸回路中。其通过在呼气阶段期间将胸内压降低至低于大气压水平和提供正压通气的手段之间循环来起作用。胸内压的降低（通常降低至-7至-9 mmHg）在胸腔内相对于身体的其余部分产生真空，从而a）增强血液返回心脏，并因此增加心输出量和血压，以及B）降低颅内压，从而增加脑灌注。本项目的目标是证明颅内压升高患者人群的临床概念证据。如果在这些II期研究中证明了显著的临床获益，ITPR有望提供一种全新的工具来增加脑灌注，从而降低颅内压升高患者（包括创伤性脑损伤和卒中患者）的发病率和死亡率。

DESCRIPTION (provided by applicant): An estimated 1.6 million head injury occurs every year in the United States. Traumatic brain injury affects 3 out of every 1000 Americans each year accounting for as many as 60,000 deaths and an estimated 70,000 to 90,000 patients with permanent neurologic disabilities. Despite advances in the treatment of patients with head injuries, traumatic brain injury is the leading cause of death and disability in children, adults in their most productive years, and our soldiers in the military. The economic consequence of these injuries in terms of both lost productivity and the cost of medical care are enormous. While the last two decades of research has resulted in a greater understanding of the physiologic events leading to secondary neuronal injury, advances are needed in the treatment of elevated intracranial pressure and decreased cerebral perfusion secondary brain injury. The applicants recently developed a novel device to decrease intracranial pressure and increase in cerebral perfusion pressures. The new non-invasive device is inserted within a standard respiratory circuit between the patient and a means to ventilate the patient (e.g. mechanical ventilator). It functions by cycling between lowering intrathoracic pressure during the expiratory phase to subatmospheric levels and providing a means to provide positive pressure ventilation. The decrease in intrathoracic pressure, typically to -7 to -9 mmHg, creates a vacuum within the thorax relative to the rest of the body thereby a) enhancing blood return to the heart and consequently increasing cardiac output and blood pressure and b) lowering intracranial pressure thereby increasing cerebral perfusion. Use of the intrathoracic pressure regulator (ITPR) is intended to significantly improve patient outcomes, based upon a unique way to increase in blood flow to the heart and brain. Phase 1 studies, the investigators 1) Established safety and proof of concept of the ITPR device in animals by demonstrating that use of the ITPR in the first hour after a substantial and potentially lethal brain injury helped to maintain metabolic stability of the brain better than standard resuscitation fluid alone; 2) Incorporated an intrathoracic pressure vacuum gauge into the ITPR system and begun work on a closed loop system by prototyping a custom digital display interface that tracks important physiological variables like intracranial pressure and intrathoracic pressure and 3) Received 510k clearance of the device. This phase 2 research application proposes to 1) Demonstrate proof of clinical concept that application of the ITPR will result in a decrease in intracranial pressure and an increase in cerebral perfusion pressure in patients with head injury in a neuro-intensive care unit; and 2) Design and prototype an enhanced, variable vacuum version of the ITPR with self-contained vacuum source and power supply for use in the OR and ICU. If a significant clinical benefit is demonstrated in these Phase 2 investigations, the ITPR promises to provide a fundamentally new tool to increase cerebral perfusion and thus reduce morbidity and mortality in patients with increased intracranial pressures, including patients who suffer from traumatic brain injury and stroke. PUBLIC HEALTH RELEVANCE: Despite advances in the treatment of patients with head injuries, traumatic brain injury (TBI) is the leading cause of death and disability in children and adults in their most productive years. It is also a leading cause of morbidity and mortality in the military. An estimated 1.6 million head injury occurs every year in the United States. Traumatic brain injury affects 3 out of every 1000 Americans each year accounting for as many as 60,000 deaths and an estimated 70,000 to 90,000 patients with permanent neurologic disabilities. Despite advances in the treatment of patients with head injuries, traumatic brain injury is the leading cause of death and disability in children, adults in their most productive years, and our soldiers in the military. The economic consequence of these injuries in terms of both lost productivity and the cost of medical care are enormous. While the last two decades of research has resulted in a greater understanding of the physiologic events leading to secondary neuronal injury, advances are needed in the treatment of elevated intracranial pressure and decreased cerebral perfusion secondary brain injury. The applicants recently developed a novel device to decrease intracranial pressure and increase in cerebral perfusion pressures. The new non-invasive device is inserted within a standard respiratory circuit between the patient and a means to ventilate the patient (e.g. mechanical ventilator). It functions by cycling between lowering intrathoracic pressure during the expiratory phase to subatmospheric levels and providing a means to provide positive pressure ventilation. The decrease in intrathoracic pressure, typically to -7 to -9 mmHg, creates a vacuum within the thorax relative to the rest of the body thereby a) enhancing blood return to the heart and consequently increasing cardiac output and blood pressure and b) lowering intracranial pressure thereby increasing cerebral perfusion. The goal of this project is to demonstrate proof of clinical concept in a patient population with elevated intracranial pressures. If a significant clinical benefit is demonstrated in these Phase 2 investigations, the ITPR promises to provide a fundamentally new tool to increase cerebral perfusion and thus reduce morbidity and mortality in patients with increased intracranial pressures, including patients who suffer from traumatic brain injury and stroke.